Macro-scale structures formed from concentrically-layered nanoscale or microscale fibers (“core-sheath fibers”) such as AxioCore® fibers commercialized by Arsenal Medical (Watertown, Mass.) are useful in a wide range of applications including drug delivery, tissue engineering, nanoscale sensors, self-healing coatings, and filters. On a commercial scale, the most commonly used techniques for manufacturing core-sheath fibers are extrusion, fiber spinning, melt blowing, and thermal drawing. None of these methods, however, are ideally suited to producing drug-loaded core-sheath fibers, as they all utilize high temperatures which may be incompatible with thermally labile materials such as drugs or polypeptides. Additionally, fiber spinning, extrusion and melt-blowing are most useful in the production of fibers with diameters greater than ten microns.
Core-sheath fibers with diameters less than 20 microns can also be produced by electrospinning, in which an electrostatic force is applied to a polymer solution to induce the formation of electrospinning jets which harden to form very fine fibers. Conventional electrospinning methods utilize a needle to supply a polymer solution, which, upon activation of an electric field, is then ejected into a continuous stream toward a grounded collector. As the jet stream travels in the air, solvent evaporation occurs resulting in a single long polymer fiber. Core-sheath fibers have been produced by electrospinning using coaxial needles, in which concentric needles are used to eject different polymer solutions: the innermost needle ejects a solution of the core polymer, while the outer needle ejects a solution of the sheath polymer.
Coaxial electrospinning has been used in the fabrication of core-sheath fibers for drug delivery in which the drug-containing layer (the “core”) is confined to the center of the fiber and is surrounded by a drug-free layer (the “sheath”). The sheath then serves as a diffusion barrier to a therapeutic agent in the core. Thus, release rates of the drug can be tightly controlled by varying the thickness, composition, and degradation profile of the sheath material as well as composition and concentration of the drug in the core Additionally, core-sheath fibers can be used for tissue engineering (e.g., incorporation of therapeutics to affect cell growth), filtration (e.g., by incorporation of self-cleaning compounds such as titanium dioxide), sensors (e.g., creation of hollow fibers to allow measurement of small analyte volumes), and as self-healing materials (e.g., spontaneous repair of surfaces with release of core contents). Core-sheath fibers can also be used as a way to create fibers from materials that would be otherwise unable to be electrospun (e.g., polymer pre-cursors such as poly(glycerol sebacic acid) or insulating materials such as Teflon). To do so, the material incompatible with electropsinning is confined in the center of the fiber and is surrounded by a material optimized for electrospinning; upon completion of the process the surrounding sheath material is removed (e.g., dissolved or melted away).
The use of a conventional coaxial needle electrospinning apparatus is depicted in FIG. 1A. The two concentric needles 110 separately deliver the core and sheath solutions—the core solution is delivered through the inner needle 112 whereas the sheath solution is delivered through the outer needle 114. A grounded collector (not shown) is placed at a distance from the needle, and a potential is generated between the collector and the concentric needles 110 with a magnitude and direction sufficient to impel both solutions from the needles in a continuous stream toward the grounded collector. Each stream forms a single core-sheath fiber, so the throughput of coaxial electrospinning methods is inherently limited by the fact that only one stream can be produced by each concentric needle pair 110.
To increase throughput, coaxial nozzle arrays have been utilized, but such arrays pose their own challenges, as separate nozzles may require separate pumps, the multiple nozzles may clog, and interactions between nozzles may lead to heterogeneity among the fibers collected. Another means of increasing throughput, which utilizes a spinning drum immersed in a bath of polymer solution, has been developed by the University of Liberec and commercialized by Elmarco, S.R.O. under the mark Nanospider®. The Nanospider® improves throughput relative to other electrospinning methods, but to date core-sheath fibers have not been fabricated using the Nanospider®.
A high-throughput approach for generating the core-sheath fibers, which has been commercialized by Arsenal Medical (Watertown, Mass.) (the “Arsenal Electrospinning Technology”), utilizes a plurality of elongate vessels with narrow apertures or slits which are aligned to co-localize different materials to multiple sites that form Taylor cones, thereby promoting the formation of multiple electrospinning jets and electrospun fibers with high throughput, as discussed in, e.g., U.S. patent application Ser. No. 13/362,467, filed on Jan. 31, 2012 (U.S. Patent App. Pub. No. 2012/0193836), the entire disclosure of which is hereby incorporated by reference.
FIG. 1B depicts an apparatus 120 implementing the Arsenal Electrospinning Technology. The apparatus 120 includes an elongate vessel 122 having one or more elongate apertures or slits 124 extending along at least a portion of the vessel 122; each slit surface includes one or more slits 126. A positive terminal of a power supply (not shown) is connected to the elongate vessel 122 directly or via a wire such that a potential difference exists between the elongate vessel 122 and a grounded collector 128. Upon application of a voltage, the core polymer solution 130 becomes charged; the charged polymer solution is acted upon by an electrostatic force impelling the core polymer solution 130 away from the elongate vessel 122 that counteracts the surface tension thereof. When the applied voltage is above a critical threshold value, Taylor cones 132 and electrospinning jets (or jets) 134 form at the exposed slit surfaces; the jets 134 are then attracted toward the collector 128, thereby forming homogeneous fibers.
The Arsenal Electrospinning Technology facilitates the manufacture of core-sheath fibers at high throughput by allowing significantly larger volumetric flow rates relative to needle-based systems 132, thus addressing a long-standing need in the field for efficient, high-throughput production of electrospun core-sheath fibers. However, further improvements in the efficiency of the Arsenal Electrospinning Technology could facilitate the use of core-sheath fibers in many applications, and could potentially significantly reduce the cost of producing such fibers.